© 2000 American Heart Association, Inc.
Editorial |
Role of Gap Junctions in Cardiac Conduction and Development
Insights From the Connexin Knockout Mice
From the Biology Department, Goddard Laboratory, University of Pennsylvania, Philadelphia, Pa.
Correspondence to Cecilia W. Lo, Biology Department, Goddard Laboratory, University of Pennsylvania, Philadelphia, PA 19104-6017. E-mail clo@sas.upenn.edu
Key Words: gap junction • connexin • conduction • septation • heart development
 |
Introduction |
|---|
Gap junctions are membrane channels that mediate the cell-to-cell movement of ions and small metabolites. In the heart, gap junctions play an important role in impulse conduction. Studies over the last decade have revealed that gap junctions are encoded by a multigene family known as the connexins. There are at least 15 connexin genes in the vertebrate genome.1 Connexins have been referred to by 2 nomenclature systems, either according to the molecular weight of the protein or by its class as determined by protein sequence.1 2 The molecular weight designation will be used here in conformity with the study by Kirchhoff et al3 in this issue of Circulation Research.
In the heart, there are 3 major connexin isotypes expressed: connexin
(Cx)43 (
1 connexin), Cx45
(6 connexin), and Cx40
(5 connexin). Each of these connexins exhibits
different channel properties and is regulated by different gating
mechanisms. Cx43 is the only connexin known to be expressed in the
adult working myocardium,4 although a recent
report suggests that Cx37 (6 connexin) also
may be present.5 In the specialized conductive tissue
of the heart, Cx45 is found in the atrioventricular
node and adjoining His bundles.6 This connexin isotype
forms voltage-sensitive channels with very low
conductance.7 In contrast, Cx40, which generates channels
with high conductance,8 is expressed in the
fast-conducting tissues of the His-Purkinje system, being nested within
the Cx45 expression domain (Figure
).9 10 In the Purkinje
fibers of the peripheral conductive tissue, Cx43 is
coexpressed with Cx40 (Figure).9 It is hypothesized
that this
This article has been cited by other articles:
 |
|
 |
|
  A. Totzeck, K. Boengler, A. van de Sand, I. Konietzka, P. Gres, D. Garcia-Dorado, G. Heusch, and R. Schulz No impact of protein phosphatases on connexin 43 phosphorylation in ischemic preconditioning Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2106 - H2112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Bakker, B. J. Boukens, M. T.M. Mommersteeg, J. F. Brons, V. Wakker, A. F.M. Moorman, and V. M. Christoffels Transcription Factor Tbx3 Is Required for the Specification of the Atrioventricular Conduction System Circ. Res., June 6, 2008; 102(11): 1340 - 1349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ruiz-Meana, A. Rodriguez-Sinovas, A. Cabestrero, K. Boengler, G. Heusch, and D. Garcia-Dorado Mitochondrial connexin43 as a new player in the pathophysiology of myocardial ischaemia-reperfusion injury Cardiovasc Res, January 15, 2008; 77(2): 325 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T.M. Mommersteeg, N. A. Brown, O. W.J. Prall, C. de Gier-de Vries, R. P. Harvey, A. F.M. Moorman, and V. M. Christoffels Pitx2c and Nkx2-5 Are Required for the Formation and Identity of the Pulmonary Myocardium Circ. Res., October 26, 2007; 101(9): 902 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. F. Bukauskas, M. M. Kreuzberg, M. Rackauskas, A. Bukauskiene, M. V. L. Bennett, V. K. Verselis, and K. Willecke Properties of mouse connexin 30.2 and human connexin 31.9 hemichannels: Implications for atrioventricular conduction in the heart PNAS, June 20, 2006; 103(25): 9726 - 9731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kreuzberg, G. Sohl, J.-S. Kim, V. K. Verselis, K. Willecke, and F. F. Bukauskas Functional Properties of Mouse Connexin30.2 Expressed in the Conduction System of the Heart Circ. Res., June 10, 2005; 96(11): 1169 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Iacobas, S. Iacobas, W. E. I. Li, G. Zoidl, R. Dermietzel, and D. C. Spray Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart Physiol Genomics, February 10, 2005; 20(3): 211 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Maass, A. Ghanem, J.-S. Kim, M. Saathoff, S. Urschel, G. Kirfel, R. Grummer, M. Kretz, T. Lewalter, K. Tiemann, et al. Defective Epidermal Barrier in Neonatal Mice Lacking the C-Terminal Region of Connexin43 Mol. Biol. Cell, October 1, 2004; 15(10): 4597 - 4608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia-Dorado, A. Rodriguez-Sinovas, and M. Ruiz-Meana Gap junction-mediated spread of cell injury and death during myocardial ischemia-reperfusion Cardiovasc Res, February 15, 2004; 61(3): 386 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Dobrzynski, V. P. Nikolski, A. T. Sambelashvili, I. D. Greener, M. Yamamoto, M. R. Boyett, and I. R. Efimov Site of Origin and Molecular Substrate of Atrioventricular Junctional Rhythm in the Rabbit Heart Circ. Res., November 28, 2003; 93(11): 1102 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Barker, R. L. Price, and R. G. Gourdie Increased Association of ZO-1 With Connexin43 During Remodeling of Cardiac Gap Junctions Circ. Res., February 22, 2002; 90(3): 317 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Barker, R. L. Price, and R. G. Gourdie Increased Association of ZO-1 With Connexin43 During Remodeling of Cardiac Gap Junctions Circ. Res., February 22, 2002; 90(3): 317 - 324. [Abstract] [Full Text] [PDF]
|
|